Abstract: Recent years have seen the tremendous new findings in microbiome (microbiota, microbial communities) research in humans and other animals. Bacteria colonies almost all surfaces of animal body and cavities, carrying out important functions in metabolism and immunities; dysbiosis (disruption of homeostatic states) however, can lead to inflammation, infection and also can contribute to diseases. During my PhD and Post-doc research, I focused on 1) ecological and evolutionary factors shaping gut microbiome in wild mouse, where I demonstrate biogeography, diet and host genetics determines the diversity of gut microbiome, and host-microbiome co-evolutions; 2) nurture and nature of gut microbiome in humans, where we investigate relative role of environmental influences versus human genome via cohort study and GWAS analysis; 3) microbiome as important intermediate in disease models, in which microbiome interacts with host genome and the cross-talk mediates the development and manifestation of the diseases.